1. Field of the Invention
The present invention relates generally to methods and kits for determining the occurrence of periodic infertility in women. More particularly, the present invention relates to the detection of a threshold level of pregnanediol glucuronide in urine which indicates that the woman will be unable to conceive until after the occurrence of menses.
For religious, ethical, and medical reasons, a significant number of women have elected against employing contraceptive drugs and devices and instead rely on natural family planning methods for birth control. Additionally, other women and couples who utilize barrier methods of contraception often wish to determine those times, when such protection is not needed. In general, natural family planning methods rely on the woman observing certain physiological indicators, such as basal body temperature and cervical mucous consistency, to determine the time of ovulation. By refraining from intercourse for an appropriate period before and after ovulation, conception can usually be avoided. Because of variations in the woman's cycle, however, reliance on basal body temperature and the appearance of the cervical mucous is not always effective, and it would therefore be desirable to have more reliable physiological indicators.
Alternative indicators have been suggested. For example, it is known that a surge in the woman's level of luteinizing hormone (LH) is predictive of ovulation. Further, it is known that the woman's levels of progesterone are elevated a short time after ovulation. Thus, it has been suggested that by first determining the occurrence of the LH surge, and subsequently determining the presence of elevated levels of pregnanediol glucuronide (PDG, a progesterone metabolite) in urine, the time during which a woman is fertile, or conversely is infertile, may be determined.
Such two-step determinations, however, suffer from certain deficiencies. For example, the LH surge does not always occur, rendering the determination of fertile and infertile periods problematic. Second, the need to perform two distinct types of measurements complicates the determination of fertility, rendering it less useful.
For these reasons, it would be desirable to provide infertility assays which are simple to perform, preferably relying on a single type of measurement. Such assays should be a highly reliable indicator of infertility, and will preferably be combined with the observation of other physiological indicators, such as menses, in order to determine the entire period of infertility.
2. Description of the Background Art
Brown et al. (1987) Am. J. Obstet. Gynecol. 157:1082-1089 describe how a woman's period of fertility may be determined based on measurements of estrogen and pregnanediol glucuronides in urine. Enzyme assays for estrogen are used to detect the beginning of the fertile period while enzyme assays for pregnanediol glucuronides are used to detect the end. The pregnanediol glucuronide assay was positive for concentrations above 5.2 .mu.mol/24 hr. (equivalent to about 1.7 .mu.g/ml based on 1500 ml of urine). Collins et al. (1981) Proc. Xth Int'l Congress on Fertility and Sterility, MTP Ltd., pp 19-33, suggests that a woman's period of fertility may be determined by first measuring luteinizing hormone or estradiol peak followed by measurement of steroid glucuronides, such as pregnanediol-3.alpha.-glucuronide. Methods for the detection of steroid glucuronides in urine are described in Samarajeewa et al. (1983) The Urinary Assay of Steroid Glucuronides: Their Value and Methodology for Clinical Chemistry, 2nd Ed., Churchill Livingston, Edinburgh pp. 414-421. A solid phase competitive colorimetric immunoassay for 5b-pregnane-3.alpha.-20.alpha.-diol glucuronide is commercially available from Monoclonal Antibodies, Inc., Mountain View, Calif., under the tradename ProgestURINE PDG Assay. The assay is described in an accompanying package insert. A radioimmunoassay for measuring pregnanediol-3-glucuronide in urine is described in Denari et al. (1981) Obstet. Gynecol. 58:5-9, where it is further described that metabolite levels in early morning urine samples have the highest correlation with serum levels of the corresponding hormone.